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Complexity of motor response to different doses of duodenal levodopa infusion in Parkinson disease.
Clin Neuropharmacol. 2012 Jan-Feb; 35(1):6-14.CN

Abstract

OBJECTIVE

The aim was to elaborately describe individual pharmacokinetic-pharmacodynamic profiles in patients with difficult-to-treat dyskinesias treated with levodopa/carbidopa intestinal gel infusion.

METHODS

A nonrandomized, partly blinded, investigator-initiated trial was conducted in 5 patients with idiopathic Parkinson disease who were difficult to keep in "on" state without dyskinesia. Levodopa/carbidopa intestinal gel (Duodopa) doses of 80% to 120% of individually and clinically optimized dosage were infused during five 4-hour periods. Pharmacokinetic profiling, blinded assessment of video recordings, and objective movement analysis were applied every 20 to 30 minutes.

RESULTS

Individual correlations between plasma levodopa concentrations and corresponding motor scores 20 to 30 minutes after the sampling time were significant in all patients (P < 0.05 and P < 0.001). Motor scores were generally stable during the 4-hour periods. The objective test revealed that motor performance was faster the more dyskinetic the patients were. Mean individual Treatment Response Scale scores were positive in 24 of the 25 steady-state periods. Dystonia was always combined with choreic dyskinesias.

CONCLUSIONS

Motor response from different doses of levodopa/carbidopa intestinal gel is in a broad sense predictable even in dyskinetic patients although major interindividual differences in dose requirement, plasma levels, and motor response are found. That motor performance was faster the more dyskinetic the patients were implies that motor performance may be better with moderate dyskinesia than with mild dyskinesia. This may explain why patients with persistent dyskinesias choose to keep their doses above the dyskinesia threshold. There is no ideal therapeutic window in such patients, but levodopa infusion offers stable motor response.

Authors+Show Affiliations

Department of Neuroscience, Neurology, Uppsala University, E-75185 Uppsala, Sweden. dag.nyholm@neuro.uu.seNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Clinical Trial
Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

22094648

Citation

Nyholm, Dag, et al. "Complexity of Motor Response to Different Doses of Duodenal Levodopa Infusion in Parkinson Disease." Clinical Neuropharmacology, vol. 35, no. 1, 2012, pp. 6-14.
Nyholm D, Johansson A, Aquilonius SM, et al. Complexity of motor response to different doses of duodenal levodopa infusion in Parkinson disease. Clin Neuropharmacol. 2012;35(1):6-14.
Nyholm, D., Johansson, A., Aquilonius, S. M., Hellquist, E., Lennernäs, H., & Askmark, H. (2012). Complexity of motor response to different doses of duodenal levodopa infusion in Parkinson disease. Clinical Neuropharmacology, 35(1), 6-14. https://doi.org/10.1097/WNF.0b013e31823b1ffd
Nyholm D, et al. Complexity of Motor Response to Different Doses of Duodenal Levodopa Infusion in Parkinson Disease. Clin Neuropharmacol. 2012 Jan-Feb;35(1):6-14. PubMed PMID: 22094648.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Complexity of motor response to different doses of duodenal levodopa infusion in Parkinson disease. AU - Nyholm,Dag, AU - Johansson,Anders, AU - Aquilonius,Sten-Magnus, AU - Hellquist,Elisabeth, AU - Lennernäs,Hans, AU - Askmark,Håkan, PY - 2011/11/19/entrez PY - 2011/11/19/pubmed PY - 2012/5/9/medline SP - 6 EP - 14 JF - Clinical neuropharmacology JO - Clin Neuropharmacol VL - 35 IS - 1 N2 - OBJECTIVE: The aim was to elaborately describe individual pharmacokinetic-pharmacodynamic profiles in patients with difficult-to-treat dyskinesias treated with levodopa/carbidopa intestinal gel infusion. METHODS: A nonrandomized, partly blinded, investigator-initiated trial was conducted in 5 patients with idiopathic Parkinson disease who were difficult to keep in "on" state without dyskinesia. Levodopa/carbidopa intestinal gel (Duodopa) doses of 80% to 120% of individually and clinically optimized dosage were infused during five 4-hour periods. Pharmacokinetic profiling, blinded assessment of video recordings, and objective movement analysis were applied every 20 to 30 minutes. RESULTS: Individual correlations between plasma levodopa concentrations and corresponding motor scores 20 to 30 minutes after the sampling time were significant in all patients (P < 0.05 and P < 0.001). Motor scores were generally stable during the 4-hour periods. The objective test revealed that motor performance was faster the more dyskinetic the patients were. Mean individual Treatment Response Scale scores were positive in 24 of the 25 steady-state periods. Dystonia was always combined with choreic dyskinesias. CONCLUSIONS: Motor response from different doses of levodopa/carbidopa intestinal gel is in a broad sense predictable even in dyskinetic patients although major interindividual differences in dose requirement, plasma levels, and motor response are found. That motor performance was faster the more dyskinetic the patients were implies that motor performance may be better with moderate dyskinesia than with mild dyskinesia. This may explain why patients with persistent dyskinesias choose to keep their doses above the dyskinesia threshold. There is no ideal therapeutic window in such patients, but levodopa infusion offers stable motor response. SN - 1537-162X UR - https://www.unboundmedicine.com/medline/citation/22094648/Complexity_of_motor_response_to_different_doses_of_duodenal_levodopa_infusion_in_Parkinson_disease_ L2 - https://doi.org/10.1097/WNF.0b013e31823b1ffd DB - PRIME DP - Unbound Medicine ER -